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The Route of the Malignant Plasma Cell in Its Survival Niche: Exploring "Multiple Myelomas"
Antonio Giovanni Solimando1,2, Matteo Claudio Da Vià3, Niccolò Bolli3,4
1Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine 'G. Baccelli', University of Bari Medical School, 70124 Bari, Italy.
Abstract:
Growing evidence points to multiple myeloma (MM) and its stromal microenvironment using several mechanisms to subvert effective immune and anti-tumor responses. Recent advances have uncovered the tumor-stromal cell influence in regulating the immune-microenvironment and have envisioned targeting these suppressive pathways to improve therapeutic outcomes. Nevertheless, some subgroups of patients include those with particularly unfavorable prognoses. Biological stratification can be used to categorize patient-, disease- or therapy-related factors, or alternatively, these biological determinants can be included in a dynamic model that customizes a given treatment to a specific patient. Genetic heterogeneity and current knowledge enforce a systematic and comprehensive bench-to-bedside approach. Given the increasing role of cancer stem cells (CSCs) in better characterizing the pathogenesis of solid and hematological malignancies, disease relapse, and drug resistance, identifying and describing CSCs is of paramount importance in the management of MM. Even though the function of CSCs is well-known in other cancer types, their role in MM remains elusive. With this review, we aim to provide an update on MM homing and resilience in the bone marrow micro milieu. These data are particularly interesting for clinicians facing unmet medical needs while designing novel treatment approaches for MM.
Insights
Multiple myeloma (MM) and its microenvironment evade immune responses. Understanding cancer stem cells (CSCs) in MM is crucial for developing new treatments against this complex hematological malignancy.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Multiple myeloma (MM) and its stromal microenvironment employ mechanisms to evade immune surveillance and anti-tumor responses.
- Tumor-stromal cells significantly influence the immune microenvironment, presenting therapeutic targets.
- Certain patient subgroups exhibit unfavorable prognoses, necessitating personalized treatment strategies.
Purpose of the Study:
- To review the current understanding of multiple myeloma homing and resilience within the bone marrow microenvironment.
- To highlight the importance of cancer stem cells (CSCs) in MM pathogenesis, relapse, and drug resistance.
- To provide an update for clinicians on unmet medical needs in MM treatment design.
Main Methods:
- Literature review focusing on MM, immune evasion, stromal microenvironment, and cancer stem cells.
- Analysis of current research on biological stratification and dynamic treatment models for MM.
- Synthesis of data on CSCs in hematological malignancies, with a focus on their elusive role in MM.
Main Results:
- Evidence suggests MM and its microenvironment actively subvert anti-tumor immune responses.
- The role of cancer stem cells (CSCs) in MM pathogenesis, relapse, and drug resistance is increasingly recognized but remains incompletely understood.
- Biological stratification and dynamic models offer potential for personalized MM treatment.
Conclusions:
- A comprehensive bench-to-bedside approach is needed to address the genetic heterogeneity of MM.
- Further research into the role of CSCs in MM is critical for improving patient outcomes.
- Understanding MM homing and resilience in the bone marrow microenvironment is key to developing novel therapeutic strategies for unmet medical needs.
